QiShenYiQi pill improves the reparative myocardial fibrosis by regulating autophagy

J Cell Mol Med. 2020 Oct;24(19):11283-11293. doi: 10.1111/jcmm.15695. Epub 2020 Sep 2.

Abstract

QiShenYiQi pill (QSYQ), a traditional Chinese medicine, is well known for improving the myocardial remodelling, but the dose-effect relationship of its intervention in the reparative myocardial fibrosis is still unclear. We investigated the effect of QSYQ on the reparative myocardial fibrosis in cardiac myosin-induced rats and explored its mechanism of action by regulating autophagy. The results indicated that QSYQ increased LVEF and LVFS, and decreased the LVEDD, LVESD, HMI, LVMI, myocardial inflammation histology score, and collagen volume fraction in a dose-dependent manner. In addition, QSYQ declined the number of autophagosomes, down-regulated the expression of myocardial Beclin-1 and LC3B, up-regulated the expression of myocardial p62 and increased the ratios of myocardial p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR. We provided evidence for that QSYQ could inhibit excessive myocardial autophagy by regulating the PI3K/Akt-mTOR pathway and can be a potential therapeutic approach in treating the cardiovascular diseases such as myocarditis and dilated cardiomyopathy.

Keywords: PI3K/Akt-mTOR pathway; autophagy; reparative myocardial fibrosis; traditional Chinese medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagosomes / drug effects
  • Autophagosomes / metabolism
  • Autophagosomes / ultrastructure
  • Autophagy / drug effects*
  • Autophagy-Related Proteins / metabolism
  • Beclin-1 / genetics
  • Beclin-1 / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • Fibrosis
  • Gene Expression Regulation / drug effects
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Inbred Lew
  • Sequestosome-1 Protein / genetics
  • Sequestosome-1 Protein / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Autophagy-Related Proteins
  • Beclin-1
  • Drugs, Chinese Herbal
  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • RNA, Messenger
  • Sequestosome-1 Protein
  • Sqstm1 protein, rat
  • qishen yiqi
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases